Efficacy and safety of erlotinib HCl, an epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor, in patients with advanced ovarian carcinoma: results from a phase II multicenter study.

The aim of this single-arm, phase II study was to estimate the tumor response rate and safety profile of erlotinib HCl (erlotinib, Tarceva, OSI-774) monotherapy in patients with refractory, recurrent, HER1/EGFR-positive epithelial ovarian tumors, who had failed prior taxane and/or platinum-based chemotherapy. Thirty-four patients received 150 mg erlotinib orally once daily for up to 48 weeks or until disease progression or dose-limiting toxicity. Two patients had partial responses, lasting 8+ and 17 weeks, giving an objective response rate of 6% (95% confidence interval [CI], 0.7-19.7%). Fifteen patients (44%) had stable disease, and 17 patients (50%) had progressive disease. Median overall survival was 8 months (95% CI, 5.7-12.7 months), with a 1-year survival rate of 35.3% (95% CI, 19.8-53.5%). Patients with rash survived significantly longer than those without (P= 0.009), correlating with rash grade. Erlotinib was generally well tolerated. The most frequent erlotinib-related adverse events were rash (68%) and diarrhea (38%). Erlotinib had marginal activity but was generally well tolerated. The safety profile appears more favorable than typically experienced with standard chemotherapeutic agents, which is encouraging in these heavily pretreated patients. Combination of erlotinib with chemotherapy or other targeted agents should be considered.

French experience of quality assessment of quantitative urinary analysis.

Since 1986, clinical biochemists from the Rhône alpes area, in collaboration with a non-profit-making association (Pro Bio Qual), have been conducting an inter-laboratory quality assurance program for quantitative urine analysis. We investigated the precision and accuracy of individual methods and measurement systems routinely used in the monthly control for 13 analytes: albumin, alpha-amylase, calcium, chloride, creatinine, glucose, magnesium, phosphorus, potassium, total protein, sodium, urea, and urate. The number of laboratories participating in the program increased from 60 in 1986 to 277 in 1999. In 1986, the greatest inter-laboratory imprecision occurred in the assay of urinary total protein, because the commonly used sulfosalicylic acid turbidimetric methods displayed poor precision. Since 1989, the increasing use of pyrogallol red or Coomasie Blue dye colorimetric methods has improved inter-laboratory precision markedly. The acceptable precision and good practicability have encouraged the general use of the pyrogallol red method. As for albumin analysis, which uses a specific immunologic method, the precision was reasonably good. Quality assessment of chloride and sodium decreased when the method performance improved for other analytes (calcium, creatinine, glucose, magnesium, phosphorus, potassium, urea, urate). This program has helped the laboratories to improve the quality of quantitative urine analysis, particularly for total protein.

Design of a privileging program for diagnostic imaging: costs and implications for a large insurer in Massachusetts.

PURPOSE: To evaluate the results of a privileging program aimed to ensure that health care providers and facilities adhere to standards of care. MATERIALS AND METHODS: Technical and professional privileging applications were mailed to more than 1,800 diagnostic imaging facilities and more than 6,000 professional providers of services to members of a health care plan. Site inspections were used to determine whether facilities met standards of care. Specialty providers were assigned a range of current procedural terminology codes for which they had privileges to bill the payer. RESULTS: Of 1,004 imaging sites inspected, 197 (20%) failed with the ability to remedy the violation, 106 (10%) failed with fundamental and serious deficiencies, and 701 (70%) passed. Site inspection pass rates varied substantially by specialty. Chiropractors and podiatrists were more likely to fail than medical and surgical specialists. A strong correlation was found between refusal to participate in the inspection and failure rate. Results suggest that reduction of the number of professional claims billed led to a 2% decline in total imaging expenditures, or a more than 10:1 return on the cost of implementing technical and professional privileging programs. CONCLUSION: Health care plans can positively influence costs and quality by developing, monitoring, and enforcing their own quality standards for diagnostic imaging.

Pelvic exenteration for adenocarcinoma of the uterine cervix.

The objective of this study was to describe and compare the outcome of patients with recurrent adenocarcinoma versus squamous cell carcinoma of the uterine cervix who have been treated with pelvic exenteration. All patients undergoing pelvic exenteration for cervical adenocarcinoma from 1955 to 1989 were identified and a retrospective review was conducted. For these 35 patients, we identified 70 controls who had exenteration for squamous cell carcinoma and who were matched for node status, year of procedure, and type of procedure. No significant difference was noted between the control group and the adenocarcinoma group for size of recurrent tumor, status of margins, presence of hydronephrosis prior to exenteration, and the time elapsed from initial diagnosis to exenteration. The two groups were compared for survival and recurrence pattern. Median patient age was 47 years (range 22-70). All patients had prior pelvic radiotherapy. Thirty patients had total pelvic exenteration and 5 had anterior exenteration. There were 3 postoperative deaths (8.6%). Median survival was 38 months for the adenocarcinoma patients and 25 months for the squamous patients (P > 0.99). The overall survival between the two sets of patients was very similar (log rank P = 0.86). There were 23 postexenteration recurrences among the adenocarcinomas (22 in which the site is known) and 32 postexenteration recurrences among the squamous patients (30 with known site). For the adenocarcinoma patients, 14 of 22 had a distant recurrence versus 14 of 30 for the squamous patients (P = 0.27). Patients with central recurrence of cervical adenocarcinoma can be successfully treated with pelvic exenteration and have survival rates similar to squamous carcinoma.

The boundaries of business: commentaries from the experts.

The World Leadership Survey, which began a worldwide dialogue on a set of important issues facing managers in the 1990s, continues with commentaries from four recognized experts, each of whom addresses the survey results from a different perspective. Kenichi Ohmae, chairman of McKinsey and Company in Tokyo, addresses "The Perils of Protectionism." Ohmae argues that the old definitions of national boundaries and corporate interests reflect obsolete economic theories. The real test of national well-being, Ohmae suggests, should be the economic welfare of a nation's citizens. Sylvia Ann Hewlett, economist and former director of the Economic Policy Council in New York, analyzes the survey in terms of "The Human Resource Deficit." According to Hewlett, four principles should guide corporate strategies in the 1990s: human resource development should move up the scale of corporate priorities; a family-friendly workplace will attract and keep talented workers; companies will take limited direct responsibility for training and education; the private sector will promote public investment in social issues. James E. Austin, the Richard P. Chapman Professor of Business at the Harvard Business School, writes about "The Developing-Country Difference." In developing countries, Austin observes, managers display attitudes and follow practices that diverge from those in developed nations. In particular, the role of government, investments in education and technology, and environmental concerns set these nations apart. Michel Crozier, president of the Centre de Sociologie des Organisations in Paris, writes about "The Changing Organization." In the 1990s, Crozier argues, managers need to break from old management theories and practice, questioning hierarchy, control, distance, access to information-the whole managerial system.

Pet turtles: a continuing international threat to public health.

The occurrence of Salmonella spp. in red-eared (Pseudemys scripta elegans) turtle eggs imported into Canada from Louisiana in June to September 1988 was examined. Of 28 lots tested, six (21%) lots from three of four exporters harbored salmonellae. Salmonella poona and Salmonella arizonae were frequently encountered in both fertile eggs and packaging moss. Turtles hatched in our laboratory from affected lots of eggs shed Salmonella in tank water for up to 11 months. Widespread use of gentamicin on turtle farms to produce Salmonella-free eggs for export apparently encouraged development of antibiotic resistance in bacterial strains. Of 37 Salmonella strains isolated in this study, 30 (81%) were gentamicin resistant. Such high levels of antibiotic-resistant salmonellae in turtle eggs pose a serious human health risk. Further marketing of turtle eggs and hatchlings should be curtailed until consistent production and distribution of Salmonella-free stocks can be assured.

Clear cell carcinoma of the ovary: a study of 59 cases.

Clear cell carcinoma of the ovary accounts for 2 to 3% of all epithelial ovarian neoplasms. Patient profiles, pathological characteristics, and results of treatment are reviewed for 59 patients. The median age was 51. Disease extent at diagnosis was as follows: stage I, 18 patients (31%); stage II, 20 patients (34%); stage III, 15 patients (25%); stage IV, 3 patients (5%); and unknown stage, 3 patients (5%). Endometriosis was identified in 13 patients (22%). Hysterectomy and bilateral salpingo-oophorectomy were performed in 47 patients (80%), unilateral salpingo-oophorectomy in 8 patients (14%), and bilateral salpingo-oophorectomy in 4 patients (7%). Radiotherapy was given to 15 patients (25%), and chemotherapy was given to 42 patients (71%). The overall 2- and 5-year survival rates were 49 and 43%. The median survival was 26 months. Patients with tumors with fewer than 10 mitoses per 10 high-power fields and less than 50% solid areas had significantly longer disease-free intervals. Clear cell tumors are usually diagnosed at an earlier disease stage than the other epithelial ovarian cancers; stage for stage, however, the prognoses are similar.

The modified radical vulvectomy with groin dissection: an eight-year experience.

Fifty-one patients were admitted to a single practice at St. Joseph's Hospital between April 1, 1978, and April 1, 1986 with a diagnosis of squamous cell carcinoma of the vulva greater than 1 mm in depth. Five advanced lesions were treated with combinations of radiation and surgery. Four patients had recurrent squamous cell carcinoma. Of 42 patients treated surgically with intention of cure, 14 were treated with complete radical vulvectomy and bilateral inguinofemoral lymphadenectomies, and 28 patients were treated with complete radical vulvectomy and bilateral inguinofemoral lymphadenectomies, and 28 patients were treated in 26 instances with bilateral inguinofemoral lymphadenectomies in one of five different excision patterns individualized to the site of primary tumor. None of the 28 patients have had a recurrence. Five had positive nodes. Eight have died of unrelated causes. Lesions in 25 cases were stage I or II and in three cases they were stage III. Modified radical vulvectomy and bilateral groin dissection is a safe approach for most patients with stage I or II and occasionally even stage III lesions.